Atomoxetine HCl is a selective norepinephrine reuptake inhibitor. It is marketed under the name STRATTERA® for the treatment of attention deficit/hyperactivity disorder (ADHD) and is available in 10 mg, 18 mg, 25 mg, 40 mg, and 60 mg dosage forms. It is a white to practically white solid, which has a solubility of 27.8 mg/ml in water.
Atomoxetine, chemically known as (R)(−)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine; has the following structure:

Atomoxetine, the (R)-(−) enantiomer of tomoxetine, is an aryloxyphenylpropylamine. It is about twice as effective as the racemic mixture and about nine times more effective than the (+)-enantiomer, as disclosed in U.S. Pat. No. 4,018,895, European Patent No. 0 052 492, and European Patent No. 0 721 777 (all by Eli Lilly and Co.)
Atomoxetine HCl may be obtained from tomoxetine that undergoes an optical resolution by any methods known in the art, such as crystallization with (S)-(+)-mandelic acid, disclosed, for example in EP Patent No. 0 052 492.
EP Patent No. 0 052 492 discloses a process for the preparation of atomoxetine HCl. In this process, (R)-(−)-tomoxetine (S)-(+)-mandelate is first basified in water to eliminate the mandelate, then extracted in diethyl ether. HCl gas is bubbled into the solution to obtain atomoxetime hydrochloride.
Similarly, U.S. Pat. No. 6,541,668 discloses a process for the preparation of atomoxetine HCl involving basifying the mandelate salt, followed by extracting with t-butyl methyl ether, removing water by azeotropic distillation, and adding hydrogen chloride.
Repetition of the processes disclosed in EP Patent No. 0 052 492 and U.S. Pat. No. 6,541,668 yielded a crystalline form of atomoxetine HCl, denominated Form A. Form A may be characterized by a powder x-ray diffraction pattern having peaks at about 13.7, 17.3, 18.7, 21.1, 22.6, 24.0, 27.3, 28.4 and 29.3±0.2 degrees two-theta, and further characterized by a powder x-ray diffraction pattern having peaks at about 8.5, 13.3, 13:7, 14.7, 17.9, 22.3, 25.0, 25.4, 25.7, 26.4, 29.8 and 32.0±0.2 degrees two-theta, substantially as depicted in FIG. 1. Form A obtained by these processes may also be characterized by an infrared absorption spectrum having peaks at about 2701, 1600, 1492, 1248, 769, 756 cm−1, and further characterized by infrared absorption spectrum having peaks at about 3057, 2056, 2857, 2741, 2456, 2408, 1893, 1773, 1476, 1452, 1460, 1391, 1357, 1308, 1287, 1202, 1189, 1175, 1165, 1118, 1068, 1048, 1023, 1011, 933, 884, 821, 769, 705, 630, 579 and 546 cm−1, substantially as depicted in FIG. 4. Form A may be further characterized by a Raman absorption spectrum substantially as depicted in FIG. 6.
Those skilled in the pharmaceutical arts understand that crystallization of an active pharmaceutical ingredient offers the best method for controlling important qualities like chemical quality, particle size, and polymorphic content. Thus, there is a need for crystal forms of atomoxetine hydrochloride and processes to produce such forms. The forms should be suitable for pharmaceutical use.